During the past few years, silver nanoparticles (AgNPs) became one of the most investigated and explored nanotechnology-derived nanostructures, given the fact that nanosilver-based materials proved to have interesting, challenging, and promising characteristics suitable for various biomedical applications. Among modern biomedical potential of AgNPs, tremendous interest is oriented toward the therapeutically enhanced personalized healthcare practice. AgNPs proved to have genuine features and impressive potential for the development of novel antimicrobial agents, drug-delivery formulations, detection and diagnosis platforms, biomaterial and medical device coatings, tissue restoration and regeneration materials, complex healthcare condition strategies, and performance-enhanced therapeutic alternatives. Given the impressive biomedical-related potential applications of AgNPs, impressive efforts were undertaken on understanding the intricate mechanisms of their biological interactions and possible toxic effects. Within this review, we focused on the latest data regarding the biomedical use of AgNP-based nanostructures, including aspects related to their potential toxicity, unique physiochemical properties, and biofunctional behaviors, discussing herein the intrinsic anti-inflammatory, antibacterial, antiviral, and antifungal activities of silver-based nanostructures.

AIM:To evaluate insulin resistance, cytolysis and nonalcoholic steatohepatitis (NASH) score (NAS) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension, treated with telmisartan vs valsartan for 20 mo. METHODS:All patients met the NCEP-ATP Ⅲ criteria for metabolic syndrome. Histology confirmed steatohepatitis, defined as a NAS greater than five up to 3 wk prior inclusion, using the current criteria. Patients with viral hepatitis, chronic alcohol intake, drug abuse or other significant immune or metabolic hepatic pathology were excluded. Subjects were randomly assigned either to the valsartan (V) group (standard dose 80 mg o.d., n = 26), or to the telmisartan (T) group (standard dose 20 mg o.d., n = 28). Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed. Neither the patient nor the medical staff was aware of treatment group allocation. Paired liver biopsies obtained at inclusion (visit 1) and end of treatment (EOT) were assessed by a single blinded pathologist, not aware of patient or treatment group. Blood pressure, BMI, ALT, AST, HOMA-IR, plasma triglycerides (TG) and total cholesterol (TC) were evaluated at inclusion and every 4 mo until EOT (visit 6). RESULTS:At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T, the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION:Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH. Telmisartan showed a higher efficacy regarding insulin resistance and histology, perhaps because of its specific PPAR-gamma ligand effect.

Double or multiple antigen labeling in IHC classically relies on the existence of primary antibodies raised in different species or of different IgG isotypes to ensure the specific labeling with the secondary detection systems. However, suitable pairs of primary antibodies are not always available or the best choice (e.g., as diagnostic tools). During the last few years, several methods have been proposed to overcome this, but none of them offers the flexibility needed for reliable double or multiple enzymatic or fluorescent IHC. We present here a procedure that elutes the antibodies after a first round of immunolabeling, which, in combination with precipitation-based detection systems, allows multiple IHC rounds even for primary antibodies raised in the same species and IgG isotype. Compared with other proposed methods, this procedure ensures a reliable enzymatic or fluorescent staining without cross-reactivity and without loss of tissue antigenicity, thus offering a flexible tool for colocalization studies and pathological diagnosis. This manuscript contains online supplemental material at http://www.jhc.org . Please visit this article online to view these materials.

Angiogenesis is involved in tumor progression of oral squamous cell carcinoma (OSCC). In this study, we have investigated by immunohistochemistry vascular endothelial growth factor (VEGF) expression in tumor cells and we have correlated VEGF expression to microvessel area, evaluated by using CD105 as a marker of endothelial cells, in bioptic specimens of 54 human OSCC. Results demonstrated that VEGF is highly expressed in OSCC tumor specimens when compared to pre-neoplastic and normal tissues, without differences between the edge and inside the tumor. Moreover, VEGF expression is reduced in poor differentiated OSCC tumors when compared to moderate and good differentiated forms, and tumor microvessel area is higher in tumors when compared to pre-neoplastic lesions and normal tissues. Finally, VEGF and CD105 may be considered as reliable markers of tumor angiogenesis and progression in OSCC, even if we did not demonstrate any correlation between VEGF expression, tumor microvascular area, clinical stage, and lymph node status.

This study aimed to evaluate the subacute effect of two types of Ag-NPs(EG-AgNPs and PVP-EG-AgNPs) on antioxidant/pro-oxidant balance in rats. Seventy Wistar rats (35 males and 35 females) were divided in 7 groups and intraperitoneally exposed for 28 days to 0, 1, 2 and 4 mg/kg bw/day EG-Ag-NPs and 1, 2 and 4 mg/kg bw/day PVP- EG-Ag-NPs. After 28 days, the blood was collected, and the total antioxidant capacity (TAC), thiobarbituric reactive species (TBARS),protein carbonyl (PROTC) levels, reduced glutathione (GSH) levels and catalase (CAT) activity were determined. EG-Ag-NPs determined protective antioxidant effects in a dose-dependent manner. The exposure to the 4 mg/kg bw/day EG-Ag-NPs determines both in males and females a significant increase in TAC and CAT and a significant decrease in TBARS and PROTC only in females. The PVP-EG-AgNPs showed a different trend compared to EG-AgNPs. At 4 mg/kg bw/day the PVP-EG-AgNPs induce increased PROTC levels and decreased GSH (males and females) and TAC levels (males). The different mechanisms of EG-AgNPs and PVP-EG-AgNPs on antioxidant-/pro-oxidant balance can be explained by the influence of coating agent used for the preparation of the nanoparticles in the formation and composition of protein corona that influence their pathophysiology in the organism.